Limonoids are heavily oxygenated, modified triterpenes dominant in Meliaceae and Rutaceae plant families. The term 'limonoid' is derived from limonin, which was first identified as the bitter constituent of Citrus seeds in 1841. This group of secondary metabolites exhibits a wide range of biological properties, including anticancer, antibacterial, antifungal, antimalarial, and antiviral activities. Significant progress on the role of limonoids as promising candidates for cancer chemoprevention and/or therapy has been achieved in particular in recent years. The aim of this review article is to discuss the recent developments on limonoids chemical aspects and biological activities with the relationship between structure and activity, supporting the new possibilities for the medicinal and/or nutraceutical use of these compounds.

An overview on chemical aspects and potential health benefits of limonoids and their derivatives.

The recent scientific literature on plant-derived agents with potential or effective use in the control of the arthropod vectors of human tropical diseases is reviewed. Arthropod-borne tropical diseases include: amebiasis, Chagas disease (American trypanosomiasis), cholera, cryptosporidiosis, dengue (hemorrhagic fever), epidemic typhus (Brill-Zinsser disease), filariasis (elephantiasis), giardia (giardiasis), human African trypanosomiasis (sleeping sickness), isosporiasis, leishmaniasis, Lyme disease (lyme borreliosis), malaria, onchocerciasis, plague, recurrent fever, sarcocystosis, scabies (mites as causal agents), spotted fever, toxoplasmosis, West Nile fever, and yellow fever. Thus, coverage was given to work describing plant-derived extracts, essential oils (EOs), and isolated chemicals with toxic or noxious effects on filth bugs (mechanical vectors), such as common houseflies (Musca domestica Linnaeus), American and German cockroaches (Periplaneta americana Linnaeus, Blatella germanica Linnaeus), and oriental latrine/blowflies (Chrysomya megacephala Fabricius) as well as biting, blood-sucking arthropods such as blackflies (Simulium Latreille spp.), fleas (Xenopsylla cheopis Rothschild), kissing bugs (Rhodnius Stal spp., Triatoma infestans Klug), body and head lice (Pediculus humanus humanus Linnaeus, P. humanus capitis De Geer), mosquitoes (Aedes Meigen, Anopheles Meigen, Culex L., and Ochlerotatus Lynch Arribalzaga spp.), sandflies (Lutzomyia longipalpis Lutz & Neiva, Phlebotomus Loew spp.), scabies mites (Sarcoptes scabiei De Geer, S. scabiei var hominis, S. scabiei var canis, S. scabiei var suis), and ticks (Ixodes Latreille, Amblyomma Koch, Dermacentor Koch, and Rhipicephalus Koch spp.). Examples of plant extracts, EOs, and isolated chemicals exhibiting noxious or toxic activity comparable or superior to the synthetic control agents of choice (pyrethroids, organophosphorous compounds, etc.) are provided in the text for many arthropod vectors of tropical diseases.

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Plant Extracts, Isolated Phytochemicals, and Plant-Derived Agents Which Are Lethal to Arthropod Vectors of Human Tropical Diseases - A Review

Background: Entomopathogenic fungi are being investigated as a new mosquito control tool because insecticide resistance is preventing successful mosquito control in many countries, and new methods are required that can target insecticide-resistant malaria vectors. Although laboratory studies have previously examined the effects of entomopathogenic fungi against adult mosquitoes, most application methods used cannot be readily deployed in the field. Because the fungi are biological organisms it is important to test potential field application methods that will not adversely affect them. The two objectives of this study were to investigate any differences in fungal susceptibility between an insecticide-resistant and insecticide-susceptible strain of Anopheles gambiae sensu stricto, and to test a potential field application method with respect to the viability and virulence of two fungal species Methods: Pieces of white polyester netting were dipped in Metarhizium anisopliae ICIPE-30 or Beauveria bassiana IMI391510 mineral oil suspensions. These were kept at 27 ± 1°C, 80 ± 10% RH and the viability of the fungal conidia was recorded at different time points. Tube bioassays were used to infect insecticide-resistant (VKPER) and insecticidesusceptible (SKK) strains of An. gambiae s.s., and survival analysis was used to determine effects of mosquito strain, fungus species or time since fungal treatment of the net. Results: The resistant VKPER strain was significantly more susceptible to fungal infection than the insecticidesusceptible SKK strain. Furthermore, B. bassiana was significantly more virulent than M. anisopliae for both mosquito strains, although this may be linked to the different viabilities of these fungal species. The viability of both fungal species decreased significantly one day after application onto polyester netting when compared to the viability of conidia remaining in suspension. Conclusions: The insecticide-resistant mosquito strain was susceptible to both species of fungus indicating that entomopathogenic fungi can be used in resistance management and integrated vector management programmes to target insecticide-resistant mosquitoes. Although fungal viability significantly decreased when applied to the netting, the effectiveness of the fungal treatment at killing mosquitoes did not significantly deteriorate. Field trials over a longer trial period need to be carried out to verify whether polyester netting is a good candidate for operational use, and to see if wild insecticide-resistant mosquitoes are as susceptible to fungal infection as the VKPER strain.

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Pyrethroid resistance in Anopheles gambiae leads to increased susceptibility to the entomopathogenic fungi Metarhizium anisopliae and Beauveria bassiana

The leaf extract of Acalypha alnifolia with different solvents - hexane, chloroform, ethyl acetate, acetone and methanol - were tested for larvicidal activity against three important mosquitoes such as malarial vector, Anopheles stephensi, dengue vector, Aedes aegypti and Bancroftian filariasis vector, Culex quinquefasciatus The medicinal plants were collected from the area around Kallar Hills near the Western Ghats, Coimbatore, India A alnifolia plant was washed with tap water and shade dried at room temperature The dried leaves were powdered mechanically using commercial electrical stainless steel blender The powder 800 g of the leaf material was extract with 25 litre of various each organic solvents such as hexane, chloroform, ethyl acetate, acetone, methanol for 8 h using Soxhlet apparatus, and filtered The crude plant extracts were evaporated to dryness in a rotary vacuum evaporator The yield of extracts was hexane (864 g), chloroform (1074 g), ethyl acetate (914 g), acetone (1002 g), and methanol (1143 g) One gram of the each plant residue was dissolved separately in 100 ml of acetone (stock solution) from which different concentrations, ie, 50, 150, 250, 350 and 450 ppm, was prepared The hexane, chloroform, ethyl acetate, acetone was moderate considerable mortality; however, the highest larval mortality was methanolic extract observed in three mosquito vectors The larval mortality was observed after 24 h exposure No mortality was observed in the control The early fourth-instar larvae of A stephensi had values of LC(50) = 19737, 17875, 16434, 14990 and 12573 ppm and LC(90) = 47760, 45921, 43507, 41620 and 39550 ppm, respectively The A aegypti had values of LC(50) = 20215, 18258, 16035, 14607 and 12855 ppm and LC(90) = 47657, 46083, 44078, 41538 and 38167 ppm, respectively The C quinquefasciatus had values of LC(50) = 19879, 17248, 15106, 14069 and 12798 ppm and LC(90) = 45873, 43066, 41878, 40883 and 38626 ppm, respectively The results of the leaf extract of A alnifloia are promising as good larvicidal activity against the mosquito vector, A stephensi, A aegypti, C quinquefasciatus Therefore, this study provides first report on the larvicidal activities against three species of mosquito vectors of this plant extracts from Southern India

Evaluation of larvicidal activity of Acalypha alnifolia Klein ex Willd. (Euphorbiaceae) leaf extract against the malarial vector, Anopheles stephensi, dengue vector, Aedes aegypti and Bancroftian filariasis vector, Culex quinquefasciatus (Diptera: Culicidae).

The search for new insecticides to control dengue fever, chikungunya, and Zika vectors has gained relevance in the past decades. The aim of the present study was to evaluate the larvicidal action of essential oils (EOs) from Thymus vulgaris , Salvia officinalis , Lippia origanoides , Eucalyptus globulus , Cymbopogon nardus , Cymbopogon martinii , Lippia alba , Pelargonium graveolens, Turnera diffusa , and Swinglea glutinosa on Aedes (Stegomyia) aegypti. The EOs were extracted by microwave-assisted hydrodistillation and characterized by gas chromatography/mass spectrometry (GC/MS). The chemical components of the EOs were identified by linear retention indices and mass spectra. Lethal concentrations (LC 50 and LC 95 ) were determined by probit analysis using larvae of Ae. aegypti between the third and the fourth instars. All EOs achieved larvicidal activity at LC 50 values lower than 115 mg/L. The lowest LC 50 value (45.73 mg/L) corresponded to T. vulgaris EO, whereas C. martinii EO showed the highest LC 50 (LC 50  = 114.65 mg/L). Some EO mixtures showed lower LC 50 than oils used individually, such as the mixtures of L. origanoides  +  S. glutinosa (LC 50  = 38.40 mg/L), T. diffusa  +  S. glutinosa (LC 50  = 63.71 mg/L), and L. alba  +  S. glutinosa (LC 50  = 48.87 mg/L). The main compounds of the EOs with highest larvicidal activity were thymol (42%) and p-cymene (26.4%).

Evaluation of the insecticidal activity of essential oils and their mixtures against Aedes aegypti (Diptera: Culicidae)

Azadirachta indica A. Juss (the neem tree), a source of limonoid insect growth regulatory (IGRs), grows well in many places in sub-Saharan Africa. We explored the potential of neem wood and bark chippings in malaria vector control by evaluating their aqueous extracts as a larvicide and growth disruptor of Anopheles gambiae s.s. (Diptera: Culicidae) under laboratory conditions. Immature stages of the mosquito were tested using WHO guidelines. Fifty percent inhibition of adult emergence (IE50) of all larval instars was obtained with <0.4 g of neem chippings in 1 liter of distilled water. For pupae, significant mortality occurred at 5 g/liter. Inhibition of pupation was seen with some larvae staying as LIVs for 9 d before dying. In addition to growth retardation, reduced reaction by larvae to visual and mechanical stimuli observed at higher neem concentrations may make them more susceptible to natural predators. There were no significant differences in the sex ratio of emerged adults or wing length of females compared with the controls. High-performance liquid chromatography of aqueous extracts showed a series of constituents of varying polarity, including the limonoids nimbin and salannin, which were quantified. Azadirachtin was not detected and the observed activities are attributed to other constituents of the chippings. Such larvicides can be particularly effective where larval habitats are relatively large and readily identifiable. Aqueous extracts of neem wood chippings can be produced locally and their use has the potential to be a low-tech component of integrated malaria vector control schemes in sub-Saharan Africa.

https://bioone.org/journals/journal-of-medical-entomology/volume-46/issue-1/033.046.0114/Laboratory-Evaluation-of-the-Aqueous-Extract-of-Azadirachta-IndicaNeem-Wood/10.1603/033.046.0114.pdf

Ahmed Hassanali

Papers

Laboratory Evaluation of the Aqueous Extract of Azadirachta Indica (Neem) Wood Chippings on Anopheles Gambiae s.s. (Diptera: Culicidae) Mosquitoes